Multidrug resistant tuberculosis threatens global TB control, and transmission is responsible for more than half of all cases. Hospitals and other congregate settings are common foci of TB transmission, including spread to patients and health care workers. In the era of multidrug and extensively drug resistant TB and HIV, the consequences of TB transmission in hospitals are deadly. In addition to the morbidity, mortality and medical costs, active TB in health care workers also leads to workforce attrition and further exposes patients to infection. There is longstanding evidence that transmission is not from TB patients on effective treatment, but from unsuspected cases, and known cases with unsuspected drug resistance. Comprehensive international guidelines encourage early diagnosis, but tend to focus on known and suspected cases, environmental controls, and personal respiratory protection. A fundamentally different approach to TB control in hospitals and other congregate settings is urgently needed. In recent years, rapid molecular tests for TB and drug resistance have emerged and are being implemented. This proposal investigates the implementation of a refocused approach to TB transmission control called FAST (Find cases Actively, Separate temporarily, and Treat effectively based on molecular drug susceptibility testing) in a busy, urban hospital in a TB endemic setting. In addition to the investigation of rapd sputum based molecular diagnostic tests, the study will evaluate whether a novel, exhaled breath test for TB can avoid the need for sputum testing by reliably excluding TB. In parallel, the study will investigate the adoption of annual tuberculin skin testing (TST) of health care workers at the hospital to measure the impact of FAST on transmission. The analyses will incorporate the RE-AIM framework to identify the critical elements of the programs that will enhance the reach, effectiveness, adoption, implementation, and maintenance of these strategies in other hospitals. Three specific aims are proposed. The first aim is to evaluate FAST for reducing treatment delay and health care workers infections. The second aim is to evaluate the acceptability and barriers to FAST and health care worker TST. The third aim is to compare the cost and cost- effectiveness of FAST relative to smear and culture for TB diagnosis, drug resistance testing, and treatment initiation. The proposed research is significant because it seeks to create safer health care facilities in high- burden, resource-limited settings by reducing TB transmission to health care workers and patients. It is innovative because it shifts the focus of hospital based TB control to active case finding and prompt treatment of patients with unsuspected pulmonary TB and unsuspected drug resistance.